A vaccine is urgently needed to prevent HIV transmission and AIDS in children born to the rapidly increasing number of HIV-infected women throughout the developing world. In addition to exposure during gestation and the process of birth, most children of HIV-infected women are exposed daily to HIV in breast milk for many months or even for several years. A vaccine to prevent AIDS in children must be safe to give at birth and must rapidly elicit virus-specific immunity in the presence of maternal antiviral antibodies to protect against the multiple exposures to HIV through breast feeding. HIV vaccines currently being evaluated in adults appear to elicit immunity too slowly to be effective in infants. This proposed project will use the SIV/neonatal rhesus macaque model of human pediatric HIV/AIDS to generate information needed to fill important gaps in developing an HIV vaccine to prevent AIDS in children. Our experiments will test the hypothesis that the protective ability of an anti-HIV/SIV pediatric vaccine is directly related to the speed with which the vaccine can elicit virus-specific immune responses in the primate neonate. The overall goals of the project are (1) to enhance the rate of vaccine induced SIV-specific immune responses in rhesus neonates and, (2) to evaluate the ability of replicating and non-replicating vaccines to generate SIV-specific immunity that can prevent, delay or substantially modify disease in SIV-infected infant macaques. To achieve these goals we propose three Specific Aims. We will determine whether an SIV vaccine regimen administered at birth can: 1) Elicit rapid, protective immunity against oral SIV infection or disease (challenge at 4 weeks of age) in rhesus neonates: a) lacking SIV antibodies or b) with passively acquired SIV antibodies (by injection of SIV hyper-immune serum). 2) Provide long-term protection against oral SIV infection or disease (challenge at 1 year of age).